A Stem-Cell Heretic Makes His Case

MIT Scientist Says Embryo Research
Is Unlikely to Lead to Cures

By

Peter Landers

Updated June 6, 2007 12:01 a.m. ET

Editor's Note: Lab Journal is a new Online Journal science column written by Journal editor Peter Landers. Each column introduces readers to a scientist working on intriguing problems in health and related fields.

Embryonic stem-cell researchers are prone to touting the potential of their work to treat all sorts of ailments, from diabetes to Parkinson's disease. Don't bet on it, says James Sherley, a stem-cell specialist himself, who has become a notable heretic in the field.

Dr. Sherley, who's embroiled in a tenure battle at the Massachusetts Institute of Technology, believes destroying a human embryo to extract stem cells is unethical. So he's chosen to work only with adult stem cells. But he says his skepticism about the therapeutic value of embryonic stem cells is rooted in science.

WSJ's Peter Landers talks to MIT associate professor James Sherley about his research on adult stem cells, his moral stand on embryonic stem cell research, and his fight for tenure. (June 6)

The 49-year-old MIT associate professor, who earned M.D. and Ph.D. degrees from Johns Hopkins University, formed his scientific view after many years studying cancer and cell division. He thinks embryonic stem cells, to be useful, would have to be turned into adult stem cells first. In that case, he asserts, there is no need to rush into research with the embryonic cells.

Which type of stem cells to use in research is a question steeped in politics. President Bush announced in 2001 that federal funds wouldn't be used for human embryonic stem-cell research, except for a few stem-cell lines created prior to the announcement. In the year ending September 2007, the National Institutes of Health expects to spend about $200 million on human adult and fetal stem cells, while human embryonic stem cells will get $37 million.

That plays to the strength of adult-cell specialists such as Dr. Sherley. Last year he received a $2.5 million "pioneer award" from the NIH to study blood-forming adult stem cells in the bone marrow.

Stem cells from embryos only a few days old have the power to turn into any organ. Thus the hope for cures: If embryonic stem cells can be coaxed to turn into pancreatic cells making insulin, for example, diabetics treated with the cells might be able to avoid regular insulin injections. In theory, the same starting line of embryonic cells could be used to create new nerve cells for the paralyzed, cardiac cells for damaged hearts and so on. Stem cells in adults, by contrast, are generally limited to replenishing the organs where they're produced.

But Dr. Sherley isn't buying the proposition that more-versatile embryonic stem cells would be easier to use in treatment. The transformation of an embryonic stem cell, he says, is a one-way street: Once one of the cells turns, say, into a pancreatic cell, it can't go back. That's different from adult stem cells, which typically divide into two -- one "differentiated" cell with a specific function and another stem cell. In this way, adult stem cells keep their own numbers steady, even as they regenerate the organ they belong to.

By contrast, tissue derived from embryonic stem cells would quickly wither away, contends Dr. Sherley, unless some of the embryonic stem cells first produced into a self-sustaining colony of adult stem cells. Or, he cautions, if the tissue stayed in a more primitive form, it would keep dividing uncontrollably and cause cancer. His conclusion: It's easiest and safest to start with adult stem cells.

Embryonic stem cells by themselves "can't cure or repair these mature tissues," he says. "They cannot serve the function they are being advertised for."

Gary Steinberg, a Stanford University professor, says it's true that embryonic stem cells may first have to be transformed into adult stem cells to have value in the brain. But he thinks there may be a sweet spot with tissue created from embryonic stem cells. The tissue would be developed enough so it's not cancerous, but still at an early stage where it could turn into many types of brain cells in just the right proportion to help stroke victims and others with brain damage.

"The beauty of these more primitive stem cells is that they're smart," says Dr. Steinberg, who is using both fetal and embryonic stem cells in research to treat brain injuries. "You're using some of the cells' own innate properties to decide what's best in that part of the body."

Dr. Sherley aims to crack that problem and find ways to make adult stem cells proliferate in a Petri dish, just as embryonic cells do. His puzzle is how to suppress the natural tendency of adult stem cells to turn into one stem cell and one differentiated cell. He wants to make the adult stem cells divide into two stem cells, so that he can grow large quantities of them.

Recently, MIT's decision to deny him tenure has preoccupied him. He went on a hunger strike for 12 days this February, accusing the biological engineering department of discriminating against him because of race.

While Dr. Sherley is still battling to get an external review of how MIT handled his tenure case, the university says it's final and vows to boot him out of his lab when his appointment expires June 30. His department says lack of scholarly papers was behind the tenure decision and racism had nothing to do with it. In a statement to WSJ.com, MIT said the department's decision was upheld by a "thorough, extensive and objective" review process.

About the Author

Peter Landers is a page-one editor at The Wall Street Journal. He previously worked as a health reporter and Tokyo correspondent for the Journal. He is a graduate of Yale University. Write to Peter Landers at peter.landers@wsj.com

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